Inflammatory autoimmune diseases typically involve a complex dysregulation of the biological system. In ongoing autoimmune diseases, in certain instances, certain proinflammatory cytokines such as TNF and IL-1 are elevated. In addition, in certain instances, immune T cells and B cells may also play a role by producing cytokines, chemokines and autoantibodies.
Activation of the immune system to the body's self molecules leads to autoimmunity. Certain inflammatory autoimmune diseases are the outcome of interactions that occur between antigen presenting cells (APC) and T cells, and between T and B cells. Certain inflammatory autoimmune disease are also the result of activation of B cells—in addition to the proinflammatory cytokine cascade. During an immune response, antigenic peptides are presented by major histocompatibility complex (MHC) molecules expressed on antigen presenting cells (APCs) to the T cell receptor expressed on T cells.
This recognition event may not fully activate T cells. In certain instances, a CD4 interaction to the MHC molecule and ‘a second or co-stimulatory’ signal (during cognate interaction of APC and T cell) may be required for T cell proliferation, cytokine production and intracellular signaling events. Interaction of CD28 and B7 molecules was identified as a second signal to activate T cells. This pathway of immune co-stimulation has a negative regulator, CTLA4, expressed on activated T cells. Treatment with a soluble receptor recombinant protein of CTLA-4 leads to inactivation of immune T and B cells.
In recent years, many other co-stimulatory molecules expressed on APC or T cells (CD40:CD40L, B7:CD28 and CTLA-4,4-IBB:4-1BBL, OX40L:OX40, B7RP1:ICOS etc.) have been shown to be involved in the activation of T cells. Some of these co-stimulatory molecules are also involved in B cell activation and antibody production.